Previous observations suggested that an early rise in breath hydrogen after lactulose (ERBHAL) may identify patients with irritable bowel syndrome (IBS) likely to respond to probiotics. Therefore, we aimed to (i) investigate whether treatment with a probiotic changes breath hydrogen response in patients with ERBHAL and (ii) whether these changes identify patients who may benefit symptomatically from probiotics. Methods:: In a randomized, double-blind, placebo-controlled trial, patients with IBS (Rome III) were randomized to either 65mL/day fermented milk product containing probiotic (FMPP) or placebo for 6weeks, followed by 6weeks open-label treatment and 6weeks withdrawal. Breath hydrogen responses to lactulose (15g) and liquid-gastric emptying time were evaluated before and at the end of each treatment period. Symptoms were measured using a 100-mm visual analog scale. Results:: Loss of ERBHAL occurred in 36 of 23 patients receiving FMPP and 41 of 22 receiving placebo (P=1.00). Amongst 40 patients who completed open-label FMPP treatment, ERBHAL was lost in a further 38 , continued in 25 , and regained in 10 . Similar variability occurred in the withdrawal phase. Variability was unrelated to changes in gastric emptying. No differences in symptom response were seen between treatment groups nor in relation to the loss or retention of ERBHAL. Conclusions:: Breath hydrogen patterns after lactulose are poorly reproducible. No FMPP-specific effects on fermentation patterns or symptoms were observed. The presence of ERBHAL is not useful to predict symptomatic response to probiotic therapy in patients with IBS.